Key result
S(+) disopyramide prolongs cardiac refractoriness, an electrophysiologic effect reversed by verapamil but not nisoldipine.
Why the study?
The stereospecific effects of disopyramide enantiomers on cardiac Purkinje fiber action potentials and their modulation by calcium channel blockers were not fully characterized.
The increase in action potential duration and refractoriness produced by disopyramide is mediated by stereospecific inhibition of outward repolarizing current by the S(+) enantiomer.
Answers are grounded in this paper and cite their sources.
Disopyramide enantiomer effects remain preclinical and should not alter prescribing; extends mechanistic insights into repolarizing currents but requires clinical confirmation.
The effect of racemic disopyramide and its enantiomers on the action potential was studied in Tyrodes (4.0 mM KCL)-superfused canine cardiac Purkinje fibers. Nonstereodependent depression of action potential amplitude and phase 0 Vmax was observed in control fibers and following pretreatment with either nisoldipine or verapamil. Stereospecific effects of the enantiomers were prominent during repolarization phases of the action potential and could be modified by pretreatment with the calcium channel blocking agents. R(-) disopyramide decreased action potential duration at 90% repolarization and shortened the effective refractory period. S(+) disopyramide increased action potential duration at 90% repolarization and prolonged refractoriness. This disparate effect of the enantiomers was eliminated following pretreatment with verapamil. Stereospecific effects on repolarization persisted when fibers were pretreated with nisoldipine, a more selective calcium channel blocking agent that lacks effects on outward plateau current. The data suggest that the increase in action potential duration and refractoriness produced by disopyramide is mediated by a stereospecific inhibition of outward repolarizing current by the S(+) enantiomer.
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Kidwell et al. (1987) studied this question. Disopyramide enantiomers vs. Control fibers was evaluated on Action potential duration and effective refractory period. S(+) disopyramide increased action potential duration and prolonged refractoriness in canine cardiac Purkinje fibers, an effect eliminated by verapamil but not nisoldipine pretreatment.
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